Evaluation of RLY5016 in Heart Failure Patients (PEARL-HF)

This study has been completed.
Sponsor:
Collaborator:
Medpace, Inc.
Information provided by (Responsible Party):
Relypsa, Inc.
ClinicalTrials.gov Identifier:
NCT00868439
First received: March 23, 2009
Last updated: May 20, 2013
Last verified: May 2013
  Purpose

The purpose of this study is to assess the effects of RLY5016 on serum potassium in heart failure patients. This study will also assess the safety and tolerability of RLY5016 in heart failure patients.


Condition Intervention Phase
Hyperkalemia
Heart Failure
Drug: Spironolactone + RLY5016
Drug: Spironolactone + Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Multicenter, Randomized, Double-blind, Placebo-Controlled, Parallel-Group, Multiple-Dose Study to Evaluate the Effects of RLY5016 in Heart Failure Patients

Resource links provided by NLM:


Further study details as provided by Relypsa, Inc.:

Primary Outcome Measures:
  • Change from baseline in serum potassium [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Safety and tolerability [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Enrollment: 105
Study Start Date: April 2009
Study Completion Date: December 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: RLY5016 Drug: Spironolactone + RLY5016
Active investigational drug
Placebo Comparator: Placebo Drug: Spironolactone + Placebo
Placebo

Detailed Description:

Double-blind, randomized, placebo-controlled, parallel-group, multiple-dose study in up to 270 congestive heart failure patients. Depending on the outcome from the initial cohort of 100 patients (Part 1), a second cohort of 170 patients may be enrolled (Part 2).

Part 1:

One hundred eligible patients will be randomly assigned to receive RLY5016 (30 g/day) or placebo for 28 days. All patients will also receive spironolactone; the initial spironolactone dose is 25 mg daily and will be increased to 50 mg daily for patients who have a serum potassium ≤ 5.1 mEq/L on treatment Day 14. Study visits will be scheduled for treatment Days 3, 7, 14, 17, 21 and 28.

A safety follow-up contact will be made 7 days after administration of last dose of study drug.

An interim analysis will be conducted after data from Part 1 are available.

Part 2:

One hundred seventy eligible patients will be randomly assigned to one of two RLY5016 treatment groups (15 or 60 g/day) or placebo for 28 days. All patients will also receive spironolactone for 28 days; the initial spironolactone dose is 25 mg daily and will be increased to 50 mg daily for patients who have a serum potassium ≤ 5.1 mEq/L on treatment Day 14. Study visits will be scheduled for treatment Days 3, 7, 14, 17, 21 and 28.

A safety follow-up contact will be made 7 days after administration of last dose of study drug.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Heart failure patients clinically indicated to receive spironolactone therapy, with serum potassium levels of 4.3 - 5.1 mEq/L AND chronic kidney disease (GFR <60 mL/min) OR documented history of hyperkalemia within the last 6 months
  • Females of child-bearing potential must be non-lactating, must have a negative serum pregnancy test at screening, and must have used a highly effective form of contraception for at least 3 months before study drug administration, during the study, and for one month after study completion
  • Male patients and/or their female partners of child-bearing potential must use a highly effective form of contraception during the study and for 3 months after study completion
  • Must sign informed consent document

Exclusion Criteria:

  • History of bowel obstruction, swallowing disorders, severe gastrointestinal disorders or major gastrointestinal surgery
  • Uncorrected hemodynamically significant primary valvular disease, known obstructive or restrictive cardiomyopathy, uncontrolled or hemodynamically unstable arrhythmia
  • Coronary-artery bypass graft, percutaneous intervention (e.g. cardiac, cerebrovascular, aortic), or major surgery including thoracic and cardiac, within 3 months prior to baseline or anticipated need during study participation
  • Heart transplant recipient, or anticipated need for transplant during study participation
  • Any of the following events having occurred within 3 months prior to baseline: unstable angina as judged by the Investigator, unresolved acute coronary syndrome, transient ischemic attack or stroke
  • Current dialysis patient, or anticipated need for dialysis during study participation
  • Prior kidney transplant, or anticipated need for transplant during study participation
  • Metastatic, late-stage or end-stage cancer with < 12 months life expectancy
  • History of alcoholism or drug/chemical abuse within 1 year
  • QTcB interval > 500 msec (Bazett's correction formula)
  • Sustained systolic blood pressure > 170 or < 90 mmHg
  • Liver enzymes (ALT, AST) > 3 times upper limit of normal
  • Use of oral cardiac medications (including loop and thiazide diuretics) that have not been stable for at least 21 days prior to baseline and are not anticipated to remain stable during study participation
  • Use of any IV cardiac medications within 21 days prior to baseline, or their anticipated need during study participation.
  • Current use of polymer-based drugs (e.g. Renagel, Kayexalate, Welchol, Colestid), other phosphate binders or potassium binders, calcium supplements, antacids (eg TUMS, Maalox), or their anticipated need during study participation
  • Use of aldosterone antagonist in the last 30 days prior to baseline, unless was discontinued due to hyperkalemia
  • Use of potassium sparing medication and/or potassium supplements in the last 30 days prior to baseline
  • Use of any investigational medication, 30 days or 5 half-lives whichever is longer, prior to baseline
  • Patients who have taken investigational product in this study, or a previous RLY5016 study
  • Inability to consume the study medication, or, in the opinion of the Investigator, inability to comply with the protocol
  • In the opinion of the Investigator, any medical condition, uncontrolled systemic disease, serious intercurrent illness, or extenuating circumstance occurring or persisting, within 30 days prior to baseline, that would significantly decrease study compliance or jeopardize the safety of the patient or affect the validity of the trial results
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00868439

  Show 58 Study Locations
Sponsors and Collaborators
Relypsa, Inc.
Medpace, Inc.
Investigators
Study Director: Yuri Stasiv, Phd Relypsa, Inc.
  More Information

Additional Information:
No publications provided by Relypsa, Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Relypsa, Inc.
ClinicalTrials.gov Identifier: NCT00868439     History of Changes
Other Study ID Numbers: RLY5016-202
Study First Received: March 23, 2009
Last Updated: May 20, 2013
Health Authority: United States: Food and Drug Administration
Czech Republic: State Institute for Drug Control
Germany: Federal Institute for Drugs and Medical Devices
Poland: Ministry of Health
Georgia: Ministry of Health
Russia: Ministry of Health of the Russian Federation
Ukraine: Ministry of Health

Keywords provided by Relypsa, Inc.:
HF
Heart failure
hyperkalemia
chronic kidney disease
prevention of hyperkalemia in heart failure patients

Additional relevant MeSH terms:
Heart Failure
Hyperkalemia
Heart Diseases
Cardiovascular Diseases
Water-Electrolyte Imbalance
Metabolic Diseases
Spironolactone
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 22, 2014